Benzoyl- and α-hydroxybenzyl-phenyl-glycosides and application thereof in therapeutics

ABSTRACT

The present invention relates to the benzoyl- and α-hydroxybenzyl-phenyl-oside derivatives of general formula: ##STR1## [in which Z is CO or CHOH, X 1 , X 2 , X 3 , X 4  and X 5 , which are identical or different, each represent an atom of hydrogen, an atom of halogen, an alkyl group with 1 to 4 carbon atoms, an alkyl group with 1 to 4 carbon atoms substituted by one or more atoms of halogen, an OH group, an alkoxy group with 1 to 4 carbon atoms, an alkoxy group with 1 to 4 carbon atoms, substituted by one or more atoms of halogen, a nitro group, a cyano group, a thiocyano group, an isothiocyano group, a NR&#39;R&#34; group (where R&#39; and R&#34;, identical or different, each represent an atom of hydrogen or an alkyl group with 1 to 4 carbon atoms) X 1  being able, in addition, to represent an --NH--CS--O--CH 3  group or an --O--C(CH 3 ) 2  CO 2  --R&#39;&#34; group (where R&#39;&#34; is an alkyl group with 1 to 4 carbon atoms and, preferably, an isopropyl group); and R represents a radical ose (the hydroxyl and amine functions of the radical ose being able to be substituted by acyl, alkyl or sulfate groups)], and to their diastereoisomers. It also relates to the method for preparing these derivatives and to their application in therapeutics.

The present invention relates, as new industrial products, to the derivatives of benzoyl-phenyl-osides and of α-hydroxybenzyl-phenyl-osides of formula (I) hereinbelow. It also relates to their method of preparation and to their application in therapeutics, particularly as anti-ulcerous agents, platelet anti-aggregant agents, antithrombotic agents and cerebral oxygenators.

In the past, it has been proposed to use phenylglycosides as agents possessing antiviral properties, cf. to this end the article by Hitoshi Arita, Carbohydrate Research 62, 143-154 (1978).

It has now been surprizingly found that compounds which are structurally different since they present in particular an additional benzoyl or α-hydroxybenzyl group with respect to the phenyl-glycosides, are particularly advantageous in the treatment of ulcers and illnesses connected with circulatory disorders, and particularly in the treatment of cerebral senescence.

The compounds according to the invention are characterised in that they are selected from the group constituted by:

(i) the compounds of general formula: ##STR2## in which:

Z represents >CO or >CHOH;

X₂, X₃, X₄ and X₅, which are identical or different, each represent an atom of hydrogen, an atom of halogen, an alkyl group with 1 to 4 carbon atoms, an alkyl group with 1 to 4 carbon atoms substituted by one or more halogen atoms (particularly a CF₃ group), an OH group, an alkoxy group with 1 to 4 carbon atoms, an alkoxy group with 1 to 4 carbon atoms substituted by one or more halogen atoms, a nitro group, a cyano group, a thiocyano group, an isothiocyano group, a NR'R" group (where R' or R", which are identical or different, each represent an atom of hydrogen or an alkyl group with 1 to 4 carbon atoms);

X₁ represents an atom of hydrogen, an atom of halogen, an alkyl group having 1 to 4 carbon atoms, an alkyl group having 1 to 4 carbon atoms substituted by one or more halogen atoms (particularly a CF₃ group), an OH group, an alkoxy group with 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms substituted by one or more atoms of halogen, a nitro group, a cyano group, a thiocyano group, an isothiocyano group, a NR'R" group (where R' and R" which are identical or different, each represent an atom of hydrogen or an alkyl group with 1 to 4 carbon atoms), an --NH--CS--O--CH₃ group or an --O--C(CH₃)₂ CO₂ -R'" group (where R'" is an alkyl group with 1 to 4 carbon atoms, and preferably an isopropyl group);

R represents a radical ose, possibly substituted, and

(ii) their diastereoisomers when Z is CHOH.

The invention also includes the acid addition salts of the compounds of formula (I) when at least one of the groups X₁, X₂, X₃, X₄, X₅ and R comprises a basic group.

The group --O--R, taking into account the structure of formula (I) given hereinabove, may be in ortho, meta or para position with respect to the group Z.

The term "ose" in the definition of the radical R here denotes any elementary glucidic, non-hydrolysable unit of empirical formula (CH₂ O)_(n). According to the invention, each hydroxyl function of the ose radical may be acylated (particularly by COCH₃), alkylated (particularly by CH₃ or CH₂ C₆ H₅) or sulfated (particularly by SO₃ NH₄, SO₃ Na or SO₃ K), and the hydroxyl function of the carbon atom in 2 position may be replaced by an amine function, itself capable of being acylated (particularly by COCH₃), alkylated (particularly by CH₃ or CH₂ C₆ H₅) or sulfated (particularly by SO₃ NH₄, SO₃ Na or SO₃ K).

Consequently, R represents in particular a glycosyl radical such as β-D-glucosyl, β-D-xylosyl, β-D-galactosyl, β-D-glucosaminyl or α-L-rhamnosyl, the hydroxyl and amine functions being able, if need be, to be substituted by acyl, alkyl or sulfate groups.

When X₁ represents an --NH--CS--O--CH₃ or --O--C(CH₃)₂ CO₂ --R'" group, such a group is advantageously in para position with respect to the group Z and, in this case, each of the groups X₂, X₃, X₄ and X₅ represents an atom of hydrogen.

Atom of halogen is understood here to mean the atom of fluorine, chlorine, bromine and iodine, the preferred halogens being fluorine, chlorine and bromine and among these latter, the most advantageous halogens from the therapeutic point of view are chlorine and bromine.

Taking into account the above definitions, the invention therefore covers the carbonyl derivatives (Z=CO) of the benzoyl-phenyl-oside type and the carbinol derivatives (Z=CHOH) of the α-hydroxybenzyl-phenyl-oside type.

Among the compounds of formula (I) which are preferred according to the invention, particular mention may be made of the oside derivatives where Z is CO or CHOH; X₁, X₂, X₃, X₄ and X₅, which are identical or different, each represent H, Cl, Br, CH₃, CF₃, OH, OCH₃, NO₂, NH₂, N(CH₃)₂, NCS, X₁ also representing in para position with respect to the group Z, an --OC(CH₃)₂ CO₂ --CH(CH₃)₂ group or an --NH--CS--OCH₃ group when X₂ =X₃ =X₄ =X₅ =H; and R represents an ose radical such as β-D-glucosyl, β-D-xylosyl, β-D-galactosyl, α-L-rhamnosyl, β-D-glucosaminyl, the atom of hydrogen of the OH groups of the oside radical being able, if need be, to be replaced by a COCH₃, CH₃, CH₂ C₆ H₅, SO₃ NH₄, SO₃ Na, SO₃ K radical and the amine function of the oside group being able to be substituted by a COCH₃ group.

The compounds of formula (I) may be prepared according to a method known per se according to a conventional reactional mechanism. Thus, a phenyl-phenol of formula: ##STR3## (where Z, X₁, X₂, X₃, X₄ and X₅ are defined as hereinabove) is subjected to osidation according to

the method of Koenig-Knorr [described in the work "The Carbohydrates, Chemistry and Biochemistry" (2nd edition, Academic Press, New York and London 1972) Vol. IA, pages 295-301] by condensation of a phenol (IIa) with a haloacyloside in the presence of a catalyst such as mercuric cyanide, Ag₂ O, AgCO₃, CdCO₃ or of a tertiary amine such as collidine;

the method of Helferich (ibidem, pages 292-294) by condensation of an acyloside with a phenol (IIa) in the presence of a Lewis acid; or

the so-called ortho-ester method (ibidem, pages 300-304).

The preferred method which is recommended is characterised in that:

(i) a derivative of phenyl-phenol of formula: ##STR4## (where Z, X₁, X₂, X₃, X₄ and X₅ are defined as indicated hereinabove and A represents H or, preferably Na, K) is reacted with an ose derivative selected from the group constituted by haloacyloses and acyloses, in an inert solvent, at a rate of 1 mole of (II) for 1.1 to 1.2 mole of

(ii) if necessary, a de-acetylation reaction is carried out by heating to reflux in a lower alcohol with 1 to 4 carbon atoms (preferably methanol) in the presence of a metallic alcoholate, preferably magnesium methylate or sodium methylate.

According to a preferred embodiment of the method which is recommended, 1 mole of derivative of phenyl-phenol (II) (where A is Na or K) is reacted at stage (i) with 1.1 to 1.2 mole of a haloacylose of formula:

    Hal--Ro                                                    (III)

(where Hal is an atom of halogen F, Cl, Br, I, and preferably Cl or Br to have an optimal yield, and R represents a radical ose where the OH and NH₂ functions are protected, preferably, by an acyl group), in an inert solvent selected from the polar or apolar solvents (such as in particular dimethylformamide, tetrahydrofuran, dioxan, methanol, ethanol, acetonitrile, nitromethane, dimethylsulfoxide and mixtures thereof with one another or with the haloalkanes, in particular the mixtures DMF--CH₂ Cl₂, DMF--CHCl₃, DMF--ClCH₂ CH₂ Cl). Acetonitrile will advantageously be used as solvent, the reaction of (II) with (III) being effected at a temperature of between 0° C. and the reflux temperature of the medium (advantageously between 0° C. and 25° C. and particularly at ambient temperature) for 10 to 40 minutes (advantageously 10 to 20 minutes for the "carbonyl" compounds Z=CO, and 20 to 30 minutes for the "carbinol" compounds Z=CHOH). The derivative obtained according to this technique is subjected, if need be, to a de-acylation reaction.

When A represents H, it is recommended to use a catalyst such as mentioned hereinabove, particularly Ag₂ O.

In addition to this process which is suitable for the synthesis of compounds I of the "carbonyl" type and of the "carbinol" type, another method may be carried out for obtaining the compounds of the "carbinol" type by reduction of the corresponding "carbonyl" derivative. This reduction reaction is carried out by reacting a compound of formula I where Z=CO with an agent selected from the group constituted by complex metallic hydrides such as LiAlH₄ and KBH₄, in an inert solvent such as ether, tetrahydrofuran and the lower alcohols, particularly methanol and ethanol, at a temperature of between 0° C. and 50° C. (preferably between 0° C. and 25° C., and in particular at ambient temperature).

The compounds of formula I where Z is CHOH may be divided into their 2 diastereoisomers according to a method known per se, particularly by fractional recrystallisation. The resolution of the mixture of the diastereoisomers may advantageously be effected (a) by dissolution of said mixture in CH₃ OH--H₂ O (1:1) v/v and recrystallisation up to constant rotatory power in CH₃ OH--H₂ O (1:1) v/v, to obtain the dextrorotatory substance, then (b) by taking up the recrystallisation filtrates in CH₃ OH--H₂ O (1:2) v/v and recrystallisation up to constant rotatory power in CH₃ OH--H₂ O (1:2) v/v, to obtain the laevorotatory substance.

According to the invention, a therapeutic composition is proposed, characterised in that it contains, in association with a physiologically acceptable excipient, at least one compound selected from the group constituted by the products of formula I, their diastereoisomers and their non-toxic salts.

The compounds of formula (I) are useful in therapeutics as anti-ulcerous agents, platelet anti-aggregant agents, atithrombotic agents or cerebral oxygenators. The compounds most interesting in therapeutics are the products of Example 1 (Code No. 163), 97 (Code No. 265), 98 (Code No. 390) and 99 (Code No. 391) which are particularly indicated as veinous antithrombotic agents, the preferred compound being the product of Example 97.

Other features and advantages of the invention will be more readily understood on reading the following examples of preparation which have been given by way of non-limiting illustration.

Preparation I Obtaining of [4-(4-nitrobenzoyl)-phenyl]-2,3,4-tri-(O-acetyl)-β-D-xylopyranoside (Code No. 236; Example 41)

In a 500 ml flask is suspended the dry phenate obtained by action of 4.1 g of sodium hydroxide on 25 g of 4'-paranitro-benzoyl-phenol in a mixture of 65 ml of DMF and 200 ml of dichloro-1,2-ethane.

The mixture is taken to reflux and 45 g of 2,3,4-tri-(O-acetyl)-1-bromo-α-D-xylopyranose are added quickly. The mixture is then heated for 3 hours at reflux. After hydrolysis, it is extracted with ethyl acetate and the organic phase is washed with sodium hydroxide at 40 g/l. It is evaporated to dryness and a yellow oil is obtained which crystallises in anhydrous ether. Finally, the mixture is recrystallised in methanol. 22 g of the expected product are thus obtained.

m.p.=150° C., α_(D) ²⁰° C. =-33.3° (c=0.9 g/l;ClCH₂ CH₂ Cl).

Preparation II Obtaining of [4-(4-nitrobenzoyl)-phenyl]-β-D-xylopyranoside Code No. 163; Example 1)

20 g of acetylated product obtained according to Preparation I are dissolved hot in 300 ml of methanol and 2 g of Mg(OCH₃)₂. The mixture is taken to reflux for 2 hours. 1 liter of methanols is then added and the mixture is reheated up to complete dissolution. The yellow solution obtained is filtered. After evaporation of the solvent, the expected product is obtained with a yield of 90%.

m.p.=200° C., α_(D) ²⁰° C. =-26.6° (c=0.6 g/l; methanol).

Preparation III Obtaining of [4-(4-nitrobenzoyl)-phenyl]-2-(N-acetyl)-β-D-glucosaminide (Code No. 207; Example 44)

In a 500 ml flask is suspended the dry phenate obtained by action of 0.540 g of NaH on 5 g of 4'-paranitrobenzoylphenol, in a mixture of 25 ml of DMF and 25 ml of dichloroethane. 8.3 g of acetochloroglucosamine are added to the reaction medium and the mixture is stirred for 3 hours at 40° C. After hydrolysis, it is extracted with ethyl acetate, washed in sodium hydroxide at 40 g/l and finally with water.

After evaporation of the solvent, an oil is obtained which precipitates in ether. The acetylated derivative obtained is recrystallised in ethyl acetate. (Yield=59%; m.p.=238° C.).

This acetylated derivative is suspended in 150 ml of methanol with 0.150 g of sodium methylate. The reaction medium is stirred for 2 hours at ambient temperature then is hydrolysed on ice. After filtration, washing with water and recrystallisation in methanol, 4.4 g (yield=80%) of the expected product are obtained.

m.p.=204° C., α_(D) ²⁰° C. =+12.5° (c:0.6 g/l, methanol).

Preparation IV Obtaining of [3-(4-trifluoromethylbenzoyl)-phenyl]-β-D-xylopyranoside (Code No. 428; Example 53)

In a 250 ml flask, the following are added in order: 9.4 g of 3-(paratrifluoromethylbenzoyl)-phenol, 15 g of acetobromoxylose, the quantity of dry silver oxide (freshly prepared by action of sodium hydroxide at 40 g/l on 14 g of silver nitrate) and 100 ml of acetonitrile. The mixture is stirred for 10-20 mins. in a nitrogen atmosphere and away from the light.

After filtration then hydrolysis, the mixture is extracted with ethyl acetate, washed with sodium hydroxide at 40 g/l then with water. After evaporation of the solvent, the mixture is recrystallised in the (1:1) v/v methanol-water mixture. 10 g (yield: 55%) of the acetylated derivative are thus obtained (m.p.=90° C.) which is taken up in 100 ml of methanol with 0.1 g of sodium methylate. The mixture is stirred for 1 hour then passed over Amberlite IR 120 H resin, filtered, then the solvent is evaporated. After recrystallisation in methanol, 5 g (yield=65%) of the expected product are obtained.

m.p.=120° C. α_(D) ²⁰° C. =-38° (c=0.5 g/l; methanol).

Preparation V Obtaining of [4-(4-chlorobenzoyl)-phenyl]-3,4,6-tri-(ammonium-sulfate)-2-N-acetyl-.beta.-D-glucosaminide (Code No. 358; Example 67)

In a nitrogen atmosphere and at -10° C., 15 g of [4-(parachlorobenzoyl)-phenyl]-2-N-acetyl-β-D -glucosaminide, 29.6 ml of pyridine and 150 ml of DMF are mixed. 12.3 ml of sulfonyl chloride are added drop by drop. After stirring of the reaction medium at ambient temperature (15°-25° C.) for 12 hours, the solution is taken to pH 9 by addition of sodium bicarbonate. After extraction with ethyl acetate, the aqueous phase is evaporated at 35° C. maximum. The product is then taken up in 400 ml of water and is filtered. The filtrate is passed three times over OC1031 resin. The alcoholic phases are then evaporated. The residue is taken up in (40:12:10:1) v/v butanol-ethanol-water-ammonia-mixture and the solution passed over a neutral alumina column. After evaporation of the solvent, 16.5 g of the expected product are obtained.

m.p.=200° C. (with decomposition), α_(D) ²⁰° C. =-2.1° (c=2.6 g/l; water).

Preparation VI Obtaining of [4-(4-nitro-α-hydroxybenzyl)-phenyl]-β-D-xylopyranoside (Code No. 265; Example 97)

10 g (26.6 millimoles) of [4-(4-nitrobenzoyl)-phenyl]-β-D-xylopyranoside (Code No. 163; Example 1; cf. Preparation II) are suspended in 200 ml of methanol then 1.56 g (26.6 millimoles) of KBH₄ is added. The reaction medium thus obtained is stirred for 2 hours at ambient temperature (15°-25° C.). The progress of the reaction of reduction is controlled by CCM [solvent: toluenemethanol (3:1) v/v]. After evaporation in vacuo of the methanol, the product is taken up in ethyl acetate then washed with water (3×50 ml). It is dried over magnesium sulfate then, after evaporation of the solvent, it is recrystallised in the (3:7) v/v methanol-water mixture. 6.5 g (yield=65%) of the expected product are obtained.

m.p.=142° C., α_(D) ²⁰° C. =-17° (c=0.5 g/l:methanol).

Preparation VII Obtaining of [4-(4-nitro-α-hydroxybenzyl)-phenyl]-2,3,4-tri-(O-acetyl)-β-D-xylopyranoside (Example 96)

In a flask protected from the light and provided with a CaCl₂ tube, 2.45 g of 4-(4-nitro-α-hydroxy-benzyl)-phenol, 3.4 g of acetobromoxylose, 2.4 g of freshly prepared silver oxide and 200 ml of acetonitrile are placed. It is stirred for half an hour at ambient temperature, then filtered on fritted glass. After hydrolysis of the filtrate, the product is extracted with ethyl acetate then washed with water. The organic phase is dried, filtered then the solvent is evaporated. An oil is obtained which is purified over a silica column [eluent: (4:1) v/v toluene-ethyl acetate]. 2 g of expected product are thus obtained (yield=40%).

m.p.=80° C., α_(D) ²⁰° C. =-25° (c=0.5 g/l; methanol).

Preparation VIII

By de-acylating the product obtained according to Preparation VII, by heating to reflux in CH₃ OH in the presence of magnesium methylate, the [4-(4-nitro-α-hydroxy-benzyl)-phenyl]-β-D-xylopyranoside (according to Preparation VI above) is obtained.

Preparation IX Separation of the dextrorotatory diastereoisomer (Code No. 390; Example 98) and laevorotatory diastereoisomer (Code No. 391; Example 99) of [4-(4-nitro-α-hydroxybenzyl)-phenyl]-β-D-xylopyranoside

40 g of the product of Example 97 (Code No. 265) are dissolved in 400 ml of the (1:1) v/v methanol-water mixture and the solution is recrystallised up to constant rotatory power. 16 g of the dextrorotatory diasteroisomer are obtained.

m.p.=162° C., α_(D) ²⁰° C. =+21° (c=0.48 g/l; methanol).

The filtrates of the preceding recrystallisation operations are taken up in 300 ml of the (1:2) v/v methanol-water mixture and the product is recrystallised up to constant rotatory power. 15 g of the laevorotatory diastereoisomer are obtained.

m.p.=158° C., α_(D) ²⁰° C. =-50° (c=0.48 g/l; methanol).

Preparation X Obtaining of [2-(4-nitrobenzoyl)-phenyl]-2,3,4-tri-(O-acetyl)-β-D-xylopyranoside (Example 141)

In a 100 ml flask, 120 mg of NaH and 10 cm³ of DMSO are introduced. After 15 minutes, 2×10⁻³ mole (486 mg) of 2'-paranitrobenzylphenol then 4×10⁻³ mole (1.3 g) of acetobromoxylose and 5 ml of DMSO are added. The mixture is stirred for 1 hour at ambient temperature (15°-20° C.). It is extracted with ether and the ethereal phase is washed with water. After evaporation of the ether, 1.57 g of the expected crude product is obtained which is chromatographed over silica column [eluent: (4:1) v/v toluene-ethyl acetate] to collect 400 mg of expected pure product (yield: 40%).

m.p. 142° C.

Preparation XI Obtaining of [2-(4-nitrobenzoyl)-phenyl]-β-D-xylopyranoside (Example 57)

According to the modus operandi described in Preparation II hereinabove, and from 50 mg of [2-(4-nitrobenzoyl)-phenyl]-2,3,4-tri-(O-acetyl)-β-D-xylopyranoside obtained according to Preparation X, the expected product is obtained with a yield of 90%.

m.p. 164° C.

A certain number of compounds of formula (I) has been shown in non-limiting manner in Table I hereinbelow (where the position of the substituents has been given arbitrarily, the numbering of the vertices of the phenyl rings being made from the central group Z). Table II hereinbelow also shows the physical properties of part of these compounds, namely the melting point (m.p.) and the rotatory power (α_(D) ²⁰° C.); for the latter, the nature of the solvent and the concentration (in g/l) have been specified.

Tables III to VII hereinbelow summarise the results of the tests (toxicity, anti-ulcerous, platelet anti-aggregant, antithrombotic and anti-hypoxic activities) undertaken on a certain number of products according to the invention. The modi operandi carried out are as follows:

Acute toxicity

The acute toxicity was studied in the mouse by the I.P. route. It is expressed in the form of DL-50 (lethal dose involving the death of half of the animals) or DL-0 (maximum non-lethal dose). The results are given in Table III.

Spontaneous aggregation

The technique used is that of Sanders described in Laboratory Animal Science 27 (No. 5), pages 757-761 (1977).

After administration at 100 mg/kg I.P. (unless specified to the contrary in Table V hereinbelow) of the product to be tested to adult male reproducing rats, two blood samples are taken, one on sodium citrate and the other on sodium citrate treated with formaldehyde at instant t=5 hours.

After centrifugation of the samples, a platelet count is made on the supernatant liquid. The spontaneous aggregation index according to Wu and Hook Stroke 6, 521-524 (1975) is expressed by the relation: ##EQU1##

The results relative to the percentage of the inhibition of the platelet aggregation are given in Table V.

Veinous thrombosis

The technique used is similar to the one described by Peterson-Zucker in Thrombo.Diath.Haemorh. 23, 1, (1970).

An occlusive thrombus is created in the interior vena cava of a rat by the combined action of an endothelial alteration and a veinous stasis for 15 mins. and 4 to 5 hours after administration of the product to be tested (100 mg/kg I.P.). The results are shown in Table VI hereinbelow.

Ulcer caused by aspirin

The experiment is carried out on male Wistar rats of 180 to 200 g. The products to be tested are administered at 100 mg/kg I.P. (unless indicated to the contrary in Table IV).

At t=0, the rats are made to fast and a first administration of the product to be tested is made.

At t=18 hours, 2 ml of an ulcer-forming suspension with 192 mg of aspirin/kg are administered per os then a second administration of the product to be tested is made.

At t=22 hours, the animals are sacrificed and the ulcers are marked as follows:

small point-like ulcers: mark 1

more extensive ulcers: mark 3

highly extensive or very deep ulcers: mark 9

This marking is standardised with respect to a control batch and to cimetidine (a reference product) to which index 1 has been allocated.

Hypoxia

The experiment is carried out on batches of 20 Swiss male mice weighing from 20 to 30 g. Each product to be tested is administered to the mice by intraperitoneal route at a dose corresponding to 1/10th of the LD-50 or at a dose of 100 mg/kg when the LD-0 is higher than or equal to 800 mg/kg. The mice are placed in a nitrogen-oxygen (95:5) v/v atmosphere. The survival time of the mice is then measured up to 15 minutes maximum.

The results shown in Table VII are expressed in percentage of survival with respect to a non-treated control batch and a batch treated with an anti-hypoxic reference product [specialty known under the trade name of "Duxil" and which is constituted by a mixture of Almitrine bis-methanesulfonate and of Raubasine in the weight ratio 3:1], the anti-hypoxic reference product being administered at the dose of 18 mg/kg I.P.

The results concerning the anti-ulcerous activity of the products of formula I are shown in Table IV hereinbelow.

The products of formula (I) may be administered, particularly by the oral route, in the form of capsules or tablets which are sugar-coated or not, each containing 0.05 to 1 g of at least one compound of formula (I) as active ingredient, and preferably 0.1 to 0.5 g, on the one hand, and by the injectable route, in the form of solutions containing from 0.05 to 0.3 g of active ingredient in 2 to 10 cm³ of distilled water, on the other hand. These galenic forms may be administered at a rate of 1 to 3 times per day.

                                      TABLE I                                      __________________________________________________________________________      ##STR5##                                                                      Ex- Code                                    Position                           ample                                                                              Number                                                                              Z   X.sub.1      X.sub.2                                                                             X.sub.3                                                                             X.sub.4                                                                            X.sub.5                                                                            OR   R                             __________________________________________________________________________     1   163  CO  4-NO.sub.2   H    H    H   H   para β-D-Xyl                  2   459  CO  3-NO.sub.2   H    H    H   H   para β-D-Xyl                  3   171  CO  4-Cl         H    H    H   H   para β-D-Xyl                  4   433  CO  4-Br         H    H    H   H   para β-D-Xyl                  5   456  CO  2-Cl         H    H    H   H   para β-D-Xyl                  6   511  CO  2-NO.sub.2   H    H    H   H   para β-D-Xyl                  7   554  CO  2-NH.sub.2   H    H    H   H   para β-D-Xyl                  8   193  CO  4-NH.sub.2   H    H    H   H   para β-D-Xyl                  9   466  CO  3-NH.sub.2   H    H    H   H   para β-D-Xyl                  10  676  CO  4-N(CH.sub.3).sub.2                                                                         H    H    H   H   para β-D-Xyl                  11  227  CO  4-CF.sub.3   H    H    H   H   para β-D-Xyl                  12  229  CO  4-CH.sub.3   H    H    H   H   para β-D-Xyl                  13  465  CO  3-CF.sub.3   H    H    H   H   para β-D-Xyl                  14  435  CO  2-CH.sub.3   H    H    H   H   para β-D-Xyl                  15  --   CO  2-OCH.sub.3  H    H    H   H   para β-D-Xyl                  16  476  CO  3-OCH.sub.3  H    H    H   H   para β-D-Xyl                  17  486  CO  4-OCH.sub.3  H    H    H   H   para β-D-Xyl                  18  262  CO  H            H    H    H   H   para β-D-Xyl                  19  228  CO  4-NO.sub.2   H    H    H   H   para β-D-Glu                  20  264  CO  4-NO.sub.2   H    H    H   H   para β-D-Gal                  21  243  CO  2-CH.sub.3   H    H    3-CH.sub.3                                                                         5-CH.sub.3                                                                         para β-D-Xyl                  22  560  CO  4-Cl         H    H    3-CH.sub.3                                                                         5-CH.sub.3                                                                         para β-D-Xyl                  23  487  CO  4-NO.sub.2   H    H    3-CH.sub.3                                                                         5-CH.sub.3                                                                         para β-D-Xyl                  24  --   CO  4-NH.sub.2   H    H    3-CH.sub.3                                                                         5-CH.sub.3                                                                         para β-D-Xyl                  25  241  CO  H            H    H    3-NO.sub.2                                                                         5-CH.sub.3                                                                         para β-D-Xyl                  26  242  CO  2-CH.sub.3   H    H    3-CH.sub.3                                                                         5-CH.sub.3                                                                         para β-D-GluNHAc              27  357  CO  4-OH         2CH.sub.3                                                                           H    3-CH.sub.3                                                                         5-CH.sub.3                                                                         para β-D-Glu                  28  572  CO  4-Cl         H    H    3-CH.sub.3                                                                         H   para β-D-Xyl                  29  457  CO  4-NO.sub.2   H    H    3-CH.sub.3                                                                         H   para β-D-Xyl                  30  --   CO  4-NH.sub.2   H    H    3-CH.sub.3                                                                         H   para β-D-Xyl                  31  431  CO  2-Cl         4-Cl H    H   H   para β-D-Xyl                  32  462  CO  2-CH.sub.3   4-CH.sub.3                                                                          6-CH.sub.3                                                                          H   H   para β-D-Xyl                  33  510  CO  3-OCH.sub.3  4-OCH.sub.3                                                                         5-OCH.sub.3                                                                         H   H   para β-D-Xyl                  34  652  CO  2-CH.sub.3   4-CH.sub.3                                                                          6-CH.sub.3                                                                          3-CH.sub.3                                                                         5-CH.sub.3                                                                         para β-D-Xyl                  35  --   CO  4-NO.sub.2   2-CH.sub.3                                                                          H    3-CH.sub.3                                                                         5-CH.sub.3                                                                         para β-D-Xyl                  36  --   CO  4-NH.sub.2   2-CH.sub.3                                                                          H    3-CH.sub.3                                                                         5-CH.sub.3                                                                         para β-D-Xyl                  37  397  CO  2-CH.sub.3   6-CH.sub.3                                                                          H    3-CH.sub.3                                                                         5-CH.sub.3                                                                         para β-D-GluNHAc              38  --   CO  4-NH.sub.2   H    H    H   H   para β-D-GluNHAc              39  --   CO  4-NH.sub.2   H    H    H   H   para β-D-Glu                  40  --   CO  4-NH.sub.2   H    H    H   H   para β-D-Gal                  41  236  CO  4-NO.sub.2   H    H    H   H   para (QAc).sub.3β-D-Xyl       42  260  CO  4-NCS        H    H    H   H   para (QAc).sub.3β-D-Xyl       43  172  CO  4-Cl         H    H    H   H   para β-D-GluNHAc              44  207  CO  4-NO.sub.2   H    H    H   H   para β-D-GluNHAc              45  430  CO  H            H    H    H   H   meta β-D-Xyl                  46  650  CO  4-NO.sub.2   H    H    H   H   meta β-D-Xyl                  47  --   CO  4-NH.sub.2   H    H    H   H   meta β-D-Xyl                  48  427  CO  4-Cl         H    H    H   H   meta β-D-Xyl                  49  432  CO  4-CH.sub.3   H    H    H   H   meta β-D-Xyl                  50  --   CO  4-CH.sub.3   H    H    4-CH.sub.3                                                                         H   meta β-D-Xyl                  51  --   CO  3-CF.sub.3   H    H    H   H   meta β-D-Xyl                  52  434  CO  2-CH.sub.3   H    H    H   H   meta β-D-Xyl                  53  428  CO  4-CF.sub.3   H    H    H   H   meta β-D-Xyl                  54  429  CO  4-OCH.sub.3  H    H    H   H   meta β-D-Xyl                  55  --   CO  H            H    H    H   H   ortho                                                                               β-D-Xyl                  56  --   CO  4-Cl         H    H    H   H   ortho                                                                               β-D-Xyl                  57  --   CO  4-NO.sub.2   H    H    H   H   ortho                                                                               β-D-Xyl                  58  --   CO  4-NH.sub.2   H    H    H   H   ortho                                                                               β-D-Xyl                  59  --   CO  2-CH.sub.3   H    H    5-Cl                                                                               H   ortho                                                                               β-D-Xyl                  60  677  CO  2-CH.sub.3   H    H    5-CH.sub.3                                                                         H   ortho                                                                               β-D-Xyl                  61  --   CO  4-NO.sub.2   H    H    5-CH.sub.3                                                                         H   ortho                                                                               β-D-Xyl                  62  --   CO  4-NH.sub.2   H    H    5-CH.sub.3                                                                         H   ortho                                                                               β-D-Xyl                  63  --   CO  4-NO.sub.2   H    H    5-Cl                                                                               H   ortho                                                                               β-D-Xyl                  64  --   CO  4-NH.sub.2   H    H    5-Cl                                                                               H   ortho                                                                               β-D-Xyl                  65  222  CO                                                                                  ##STR6##    H    H    H   H   para β-D-Xyl                  66  289  CO                                                                                  ##STR7##    H    H    H   H   para β-D-Xyl                  67  358  CO  4-Cl         H    H    H   H   para (SO.sub.3 NH.sub.4).sub.3                                                      β-D-                                                                      GluNHAc                       68  416  CO  2-CH.sub.3   H    H    3-CH.sub.3                                                                         5-CH.sub.3                                                                         para (SO.sub.3 NH.sub.4).sub.3                                                      β-D-                                                                      GluNHAc                       69  488  CO  2-CH.sub.3   H    H    H   H   para (OAc).sub.3β-D-Xyl       70  490  CO  2-Cl         H    H    H   H   para (QAc).sub.3β-D-Xyl       71  497  CO  2-CH.sub.3   4-CH.sub.3                                                                          6-CH.sub.3                                                                          H   H   meta β-D-Xyl                  72  498  CO  3-NO.sub.2   H    H    H   H   para (OSO.sub.3 Na).sub.3.beta                                                      .-D-Xyl, 3H.sub.2 O           73  499  CO  2-CH.sub.3   4-CH.sub.3                                                                          6-CH.sub.3                                                                          H   H   para (OAc).sub.3β-D-Xyl       74  500  CO  2-Cl         4-Cl H    H   H   para (OAc).sub.3β-D-Xyl       75  501  CO  4-Br         H    H    H   H   para (OAc).sub.3β-D-Xyl       76  502  CO  4-CH.sub.3   H    H    H   H   para (OAc).sub.3β-D-Xyl       77  503  CO  4-NH.sub.2   H    H    H   H   para (OAc).sub.3β-D-Xyl       78  518  CO  2-NO.sub.2   H    H    H   H   para (OAc).sub.3β-D-Xyl       79  519  CO  3-OCH.sub.3  4-OCH.sub.3                                                                         5-OCH.sub.3                                                                         H   H   para (OAc).sub.3β-D-Xyl       80  520  CO  3-NO.sub.2   H    H    H   H   para (OAc).sub.3β-D-Xyl       81  521  CO  4-OCH.sub.3  H    H    H   H   para (OAc).sub.3β-D-Xyl       82  522  CO  4-Cl         H    H    H   H   meta (OAc).sub.3β-D-Xyl       83  523  CO  H            H    H    H   H   meta (OAc).sub.3β-D-Xyl       84  525  CO  3-OCH.sub.3  4-OH 5-OCH.sub.3                                                                         H   H   para (OAc).sub.3β-D-Xyl       85  477  CO  2-CH.sub.3   H    H    3-CH.sub.3                                                                         H   para β-D-Xyl                  86  512  CHOH                                                                               2-Cl         4-Cl H    H   H   para β-D-Xyl                  87  513  CHOH                                                                               3-NO.sub.2   H    H    H   H   para β-D-Xyl                  88  514  CHOH                                                                               2-Cl         H    H    H   H   para β-D-Xyl                  89  515  CHOH                                                                               2-CH.sub.3   H    H    H   H   para β-D-Xyl                  90  516  CHOH                                                                               4-CH.sub.3   H    H    H   H   para β-D-Xyl                  91  517  CHOH                                                                               4-Cl         H    H    H   H   para β-D-Xyl                  92  526  CHOH                                                                               H            H    H    H   H   para β-D-Xyl                  93  527  CHOH                                                                               3-CF.sub.3   H    H    H   H   para β-D-Xyl                  94  528  CHOH                                                                               4-Cl         H    H    H   H   para β-D-Xyl                  95  529  CHOH                                                                               4-Br         H    H    H   H   para β-D-Xyl                  96  559  CHOH                                                                               4-NO.sub.2   H    H    H   H   para (OAc).sub.3β-D-Xyl       97 (a)                                                                             265  CHOH                                                                               4-NO.sub.2   H    H    H   H   para β-D-Xyl                  98 (b)                                                                             390  CHOH                                                                               4-NO.sub.2   H    H    H   H   para β-D-Xyl                  99 (c)                                                                             391  CHOH                                                                               4-NO.sub.2   H    H    H   H   para β-D-Xyl                  100 411  CHOH                                                                               4-Cl         H    H    H   H   para β-D-GluNHAc              101 555  CHOH                                                                               2-NO.sub.2   H    H    H   H   para β-D-Xyl                  102 551  CO  2-Cl         H    H    3-CH.sub.3                                                                         5-CH.sub.3                                                                         para β-D-Xyl                  103 550  CO  2-CH.sub.3   H    H    3-CH.sub.3                                                                         H   para (OAc).sub.3β-D-Xyl       104 549  CO  4-NO.sub.2   H    H    3-CH.sub.3                                                                         H   para (OAc).sub.3β-D-Xyl       105 558  CHOH                                                                               2-CH.sub.3   H    H    3-CH.sub.3                                                                         H   para β-D-Xyl                  106 (d)                                                                            557  CHOH                                                                               4-CH.sub.3   H    H    H   H   meta β-D-Xyl                  107 (d)                                                                            556  CHOH                                                                               4-CH.sub.3   H    H    H   H   meta β-D-Xyl                  108 541  CO  3-CF.sub.3   H    H    H   H   para (OAc).sub.3β-D-Xyl       109 561  CO  4-NO.sub.2   H    H    H   H   para (OAc).sub.3β-DGluNHa                                                      c                             110 562  CO  4-NO.sub.2   H    H    H   H   para (OAc).sub.4β-DGlu        111 563  CO  4-CH.sub.3   H    H    H   H   para βDGlu NHAc               112 564  CO  4-CH.sub.3   H    H    H   H   para (OAc).sub.3 βDGlu                                                         NHAc                          113 565  CO  2-Cl         H    H    3-CH.sub.3                                                                         5-CH.sub.3                                                                         para (OAc).sub.3 βD Xyl       114 566  CO  4-Cl         H    H    3-CH.sub.3                                                                         5-CH.sub.3                                                                         para (OAc).sub.3 βD Xyl       115 662  CHOH                                                                               4-NO.sub.2   H    H    H   H   para β-D-Gal                  116 568  CO  4-N(CH.sub.3).sub.2                                                                         H    H    H   H   para (OAc).sub.3 βD Xyl       117 570  CHOH                                                                               H            H    H    H   H   meta β-D Xyl                  118 573  CO  4-CF.sub.3   H    H    H   H   para β-D-GluNHAc              119 574  CO  4-NO.sub.2   H    H    3-CH.sub.3                                                                         5-CH.sub.3                                                                         para β-D-GluNHAc              120 575  CO  2-Cl         H    H    H   H   para β-D-GluNHAc              121 576  CO  2-CH.sub.3   H    H    H   H   para β-D-GluNHAc              122 583  CO  2-CH.sub.3   H    H    3-CH.sub.3                                                                         H   para β-D-GluNHAc              123 589  CHOH                                                                               4-NO.sub.2   H    H    H   H   para β-D-GluNHAc              124 590  CO  4-Cl         H    H    H   H   para β-D-Glu                  125 591  CO  2-OH         H    H    H   H   para β-D-Xyl                  126 602  CO  H            H    H    H   H   para β-D-Glu                  127 605  CO  4-CH.sub.3   H    H    H   H   para β-D-Glu                  128 618  CHOH                                                                               4-CH.sub.3   H    H    H   H   para β-D-Glu NHAc             129 619  CHOH                                                                               4-NO.sub.2   H    H    H   H   para β-D-Glu                  130 620  CO  N            H    H    H   H   para β-D-Glu NHAc             131 621  CHOH                                                                               4Cl          H    H    H   H   para β-D-Glu                  132 680  CO  3-CF.sub.3   H    H    H   H   meta β-D-Xyl                  133 651  CHOH                                                                               4CH.sub.3    H    H    H   H   para β-D-Glu                  134 653  CHOH                                                                               H            H    H    H   H   para β-D-Glu                  135 679  CO  4-CH.sub.3   H    H    4-CH.sub.3                                                                         H   meta β-D-Xyl                  136 678  CHOH                                                                               4-NO.sub.2   H    H    H   H   ortho                                                                               β-D-Xyl                  137 --   CO  4-Cl         H    H    H   H   para β-D-Gal                  138 --   CHOH                                                                               4-NH.sub.2   H    H    H   H   para β-D-Gal                  139 --   CO  4-NO.sub.2   H    H    H   H   para α-L-Rham                140 --   CO  H            H    H    2-CH.sub.3                                                                         H   para β-D-Xyl                  141 --   CO  4-NO.sub.2   H    H    H   H   ortho                                                                               (OAc).sub.3β-D-Xyl       __________________________________________________________________________      Notes:                                                                         (a) mixture of the two diastereoisomers                                        (b) dextrogyre diastereoisomer                                                 (c) laevogyre diastereoisomer                                                  (d) Example compounds 106 and 107 are diastereoisomers (see optical            rotation values in Table II)                                             

                                      TABLE II                                     __________________________________________________________________________     PHYSICAL PROPERTIES                                                                         Melting Point                                                                              OPTICAL ROTATION                                      Example                                                                             Code Number                                                                            (° C.)                                                                              α.sub.D.sup.20° C.                                                     Concentration                                                                          Solvent                                  __________________________________________________________________________     1    163     200         -26.6                                                                               0.6     MeOH                                     2    459     135         -30  0.15    MeOH                                     3    171     174         -27.04                                                                              1.054   MeOH                                     4    433     182         -23.8                                                                               0.84    MeOH                                     5    456     90          -21  0.7     MeOH                                     6    511     130         -23  0.5     MeOH                                     8    193     200         -26.5                                                                               0.49    MeOH                                     9    466     150         -26  0.3     MeOH                                     10   676     205         -47  0.5     MeOH                                     11   227     160         -25.4                                                                               0.61    MeOH                                     12   229     162         -26.7                                                                               0.6     MeOH                                     13   465     100         -26  0.35    MeOH                                     14   435     125         -21  0.5     MeOH                                     15   --      126         -6.8 0.5     MeOH                                     16   476     154         -30  0.5     MeOH                                     17   486     180         -26  0.5     MeOH                                     18   262     140         -20  0.7     AcOEt                                    19   228     196         -54.2                                                                               0.6     MeOH                                     20   264     220         -39.34                                                                              0.61    Pyridine                                 21   243     132         +17.25                                                                              0.58    MeOH                                     22   560     188         +32  0.5     MeOH                                     23   487     185         +13  0.25    MeOH                                     25   241     100         -83.3                                                                               0.63    MeOH                                     26   242     >265        -9.4 0.6     Pyridine                                 27   357     222         -12.8                                                                               0.7     Pyridine                                 29   457     200         -27  0.2     MeOH                                     31   431     172         -21.5                                                                               0.72    MeOH                                     32   462     130         -24  0.5     MeOH                                     33   510     170         -22  0.5     MeOH                                     37   397     220         +17  0.2     MeOH                                     41   236     150         -33.3                                                                               0.9     ClCH.sub.2 CH.sub.2 Cl                   42   260     143         --   --      --                                       43   172     240         -8.8 0.91    Pyridine                                 44   207     206         +12.5                                                                               0.6     MeOH                                     45   430     140         -30  0.5     MeOH                                     46   650     108         -29.6                                                                               0.5     MeOH                                     48   427     80          -25.5                                                                               0.7     MeOH                                     49   432     154         -28.6                                                                               0.77    MeOH                                     52   434     168         -32.5                                                                               0.8     MeOH                                     53   428     120         -38  0.5     MeOH                                     54   429     140         -27  0.7     MeOH                                     56   --      129.5       --   --      --                                       57   --      164         --   --      --                                       60   677     187         -68  0.6     acetone                                  66   289     144         -22.13                                                                              0.61    MeOH                                     67   358     200 (with decomposition)                                                                   -2.1 2.6     H.sub.2 O                                68   416     >265        +11  1       H.sub.2 O                                69   488     115         - 22 0.52    MeOH                                     70   490     165         -24  0.5     MeOH                                     71   497     220         -33  0.5     MeOH                                     72   498     --          -40  0.2     MeOH                                     73   499     153         -45  0.5     MeOH                                     74   500     140         -20  0.5     MeOH                                     75   501     150         -12  0.5     MeOH                                     76   502     138         -22  0.5     MeOH                                     77   503     170         -17  0.5     MeOH                                     78   518     145         -25  0.5     MeOH                                     79   519     114         -16  0.5     MeOH                                     80   520     145         -26  0.5     MeOH                                     81   521     144         -21  0.5     MeOH                                     82   522     126         -26  0.5     MeOH                                     83   523     148         -28  0.5     MeOH                                     84   525     162         -48  0.5     MeOH                                     85   477     135         -25  0.5     MeOH                                     86   512     152         -16.7                                                                               0.54    MeOH                                     87   513     125         -15  0.5     MeOH                                     88   514     210         -23  0.5     MeOH                                     89   515     210         -26  0.5     MeOH                                     90   516     206         -24  0.5     MeOH                                     91   517     185         -16  0.5     MeOH                                     92   526     190         -26  0.5     MeOH                                     93   527     168         -20  0.5     MeOH                                     94   528     84          -37  0.5     MeOH                                     95   529     190         -23  0.5     MeOH                                     96   559     80          -25  0.5     MeOH                                     97   265     142         -17  0.5     MeOH                                     98   390     162         +21  0.48    MeOH                                     99   391     158         -50  0.48    MeOH                                     100  411     218         +13  0.5     MeOH                                     101  555     198         -45  0.5     MeOH                                     102  551     190         +13  0.5     MeOH                                     103  550     102         -33  0.5     MeOH                                     104  549     164         -46  0.5     CHCl.sub.3                               105  558     110         -9.5 0.42    MeOH                                     106  557     50          -24  0.41    MeOH                                     107  556     50          -11  0.45    MeOH                                     108  541     140         -27  0.5     MeOH                                     109  561     240         -64  0.50    CHCl.sub.3                               110  562     218         --   --      --                                       111  563     212         +25  0.20    EtOH                                     112  564     220         -12.7                                                                               0.55    CHCl.sub.3                               113  565     130         -8   0.50    CHCl.sub.3                               114  506     150         +40  0.50    CHCl.sub.3                               115  662     172         --   --      --                                       116  568     152         --   --      --                                       117  570     180         -2.3 0.44    MeOH                                     118  573     238         +20  0.40    MeOH                                     119  574     268         --   --      --                                       120  575     226         +20  0.40    MeOH                                     121  576     230         +22  0.50    MeOH                                     122  583     238         +4   0.50    MeOH                                     123  589     215         +20  0.50    MeOH                                     124  590     152         --   --      --                                       125  591     180         -60  0.40    MeOH                                     126  602     163         -54  0.5     MeOH                                     127  605     110         -55  0.48    MeOH                                     128  618     210         +72  0.2     EtOH--H.sub.2 O (4:1)v/v                 129  619     140         -66  0.5     MeOH                                     130  620     250         +20  0.5     MeOH                                     131  621     130         -64  0.5     MeOH                                     132          135         -66  0.5     MeOH                                     133  651     84          -26.4                                                                               0.72    MeOH                                     134  653     90          -43.8                                                                               0.48    MeOH                                     135  679     125         -66  0.6     MeOH                                     136  678     207         --   --      --                                       137  --      202         --   --      --                                       138  --      Decomposition                                                                              --   --      --                                                    at 60° C.                                                  139  --      94                                                                140  --      110         -61  0.3     MeOH                                     141  --      142         --   --      --                                       __________________________________________________________________________

                  TABLE III                                                        ______________________________________                                         Acute toxicity in mice per I.P. route                                                                    DL-0; DL-50                                          Example   Code Number     mg/kg IP                                             ______________________________________                                         1         163             DL-0 > 800                                           2         459             DL-0 > 800                                           3         171             DL-0 > 800                                           4         433             DL-0 > 800                                           5         456             DL-0 > 800                                           6         511             DL-50 = 600                                          7         554             DL-0 > 800                                           8         193             DL-0 > 800                                           11        227             DL-0 > 800                                           12        229             DL-0 > 800                                           13        465             DL-50 = 170                                          14        435             DL-50 = 740                                          16        476             DL-0 > 800                                           17        486             DL-50 = 1600                                         18        262             DL-50 > 1000                                         19        228             DL-0 > 800                                           20        264             DL-0 > 800                                           21        243             DL-50 = 600                                          22        560             DL-50 = 500                                          23        487             DL-50 = 750                                          25        241             DL-50 = 330                                          26        242             DL-50 = 700                                          27        357             DL-0 > 800                                           28        572             DL-0 > 800                                           29        457             DL-0 > 800 - 31 431 DL-0 > 800                       32        462             DL-0 > 800                                           33        510             DL-0 > 800                                           37        397             DL-50 = 600                                          41        236             DL-0 > 800                                           42        260             DL-0 > 800                                           43        172             DL-0 > 800                                           44        207             DL-0 > 800                                           45        430             DL-0 > 800                                           48        427             DL-50 = 220                                          49        432             DL-0 > 800                                           52        434             DL-0 > 800                                           53        428             DL-50 = 550                                          54        429             DL-0 > 800                                           65        222             DL-0 > 800                                           67        358             DL-0 > 800                                           68        416             DL-0 > 800                                           69        488             DL-50 = 900                                          70        490             DL-0 > 800                                           71        497             DL-0 > 800                                           72        498             DL-50 = 650                                          73        499             DL-0 > 800                                           74        500             DL-0 > 800                                           75        501             DL-0 > 800                                           76        502             DL-0 > 800                                           77        503             DL-0 > 800                                           78        518             DL-0 > 800                                           79        519             DL-0 > 800                                           80        520             DL-0 > 800                                           81        521             DL-0 > 800                                           82        522             DL-0 > 800                                           83        523             DL-0 > 800                                           84        525             DL-0 > 800                                           85        477             DL-50 > 550                                          86        512             DL-50 > 350                                          87        513             DL-50 > 600                                          88        514             DL-0 > 800                                           89        515             DL-0 > 800                                           90        516             DL-0 > 800                                           91        517             DL-0 > 800                                           92        526             DL-50 = 1400                                         93        527             DL-0 > 800                                           94        528             DL-50 = 330                                          95        529             DL-0 > 800                                           97        265             DL-50 > 1000                                         100       411             DL-0 > 800                                           101       555             DL-0 > 800                                           102       551             DL-0 > 800                                           103       550             DL-0 > 800                                           104       549             DL-0 > 800                                           105       558             DL-50 = 450                                          106       557             DL-50 = 500                                          107       556             DL-50 = 550                                          108       541             DL-0 > 800                                           109       561             DL-0 > 800                                           110       562             DL-0 >  800                                          111       563             DL-50 = 750                                          112       564             DL-0 > 800                                           113       565             DL-50 = 630                                          114       566             DL-0 > 800                                           116       568             DL-0 > 800                                           117       570             DL-50 = 1000                                         118       573             DL-0 > 800                                           119       574             DL-0 > 800                                           120       575             DL-0 > 800                                           121       576             DL-0 > 800                                           122       583             DL-0 > 800                                           123       589             DL-0 > 800                                           124       590             DL-0 > 800                                           125       591             DL-50 = 1700                                         126       602             DL-0 > 800                                           127       605             DL-50 = 700                                          128       618             DL-0 > 800                                           129       619             DL-0 > 800                                           130       620             DL-0 > 800                                           131       621             DL-50 = 730                                          ______________________________________                                    

                  TABLE IV                                                         ______________________________________                                         Anti-ulcer activity                                                            Example    Code Number Ulcer index                                             ______________________________________                                         1          163         0.56                                                    2          459         0.84                                                    4          433         1.04                                                    6          511         0.45                                                    8          193         0.25                                                    11         227         0 (200 mg/kg P.O.)                                      12         229         0.26                                                    13         465         0.46                                                    16         476         0.73                                                    17         486         0.69                                                    19         228         0.74                                                    20         264         0.62                                                    21         243         0.16                                                    22         560         1.46                                                    23         487         0.52                                                    25         241         0.54                                                    26         242         0.60                                                    27         357         0.42                                                    31         431         1.04                                                    32         462         0.54                                                    33         510         0.46                                                    37         397         1.02                                                    41         236         0.40                                                    43         172         0.52                                                    44         207          0.385                                                  45         430         1.11                                                    48         427         0.75                                                    49         432         1.21                                                    53         428         0.64                                                    54         429         0.57                                                    67         358         0.81                                                    69         488         0.78                                                    70         490         0.56                                                    71         497         0.98                                                    72         498         0.47                                                    73         499         0.52                                                    74         500         0.91                                                    75         501         0.32                                                    76         502         0.38                                                    80         520         1.00                                                    81         521         0.64                                                    86         512         0.50                                                    87         513         0.35                                                    88         514         0.39                                                    89         515         0.88                                                    90         516         0.57                                                    91         517         0.72                                                    95         529         0.52                                                    97         265         0.52                                                    100        411         0.35                                                    101        555         0.56                                                    102        551         0.49                                                    103        550         0.65                                                    104        549         0.84                                                    108        541         0.30                                                    109        561         0.65                                                    110        562         0.71                                                    111        563         0.42                                                    112        564         0.68                                                    116        568         0.44                                                    117        570         0.59                                                    118        573         0.53                                                    119        574         0.47                                                    121        576         0.39                                                    122        583         0.91                                                    ______________________________________                                    

                  TABLE V                                                          ______________________________________                                         Blood platelet anti-aggregation activity                                                                Inhibition of platelet                                                         aggregation                                           Example  Code Number     (a)                                                   ______________________________________                                         1        163             ++                                                    8        193             ++                                                    12       229             +                                                     14       435             ++ (75 mg/kg IP)                                      21       243             ++                                                    54       429             ++                                                    67       358             +                                                     79       519             ++                                                    94       529             + (33 mg/kg IP)                                       97       265             ++                                                    102      551             ++                                                    104      549             ++                                                    105      558             + (45 mg/kg IP)                                       113      565             ++ (63 mg/kg IP)                                      114      566             +                                                     118      573             +                                                     ______________________________________                                          Note                                                                           (a) the inhibition percentage of blood platelet aggregation corresponds t      the following notation:                                                        + inhibition of 25 to 39%                                                      ++ inhibition higher than or equal to 40%                                

                  TABLE VI                                                         ______________________________________                                         Veinous anti-thrombus activity                                                                         Diminution of - Example Code Number veinous                                    thrombus (a)                                           ______________________________________                                         2        459            +                                                      3        171            +                                                      4        433            +                                                      5        456            ++                                                     6        511            +                                                      7        554            ++                                                     8        193            ++                                                     14       435            ++                                                     17       486            +                                                      18       262            +                                                      23       487            +                                                      29       457            +                                                      45       430            +                                                      54       429            +                                                      67       358            +                                                      69       488            +                                                      70       490            +                                                      71       497            +                                                      75       501            +                                                      76       502            +                                                      77       503            +                                                      81       521            +                                                      85       477            ++                                                     86       512            +                                                      87       513            ++                                                     88       514            ++                                                     89       515            ++                                                     91       517            +                                                      92       526            +                                                      97       265            ++                                                     98       390            ++                                                     99       391            +                                                      101      555            ++                                                     102      551            +                                                      106      557            ++ (50 mg/kg IP)                                       108      541            +                                                      119      574            ++                                                     123      589            +                                                      125      591            +                                                      130      620            +                                                      131      621            +                                                      ______________________________________                                          Note                                                                           (a) notation:                                                                  + inhibition of 30 to 49%                                                      ++ inhibition higher than or equal to 50%                                

                  TABLE VII                                                        ______________________________________                                         Anti-hypoxic activity                                                          Example     Code Number    Survival (a)                                        ______________________________________                                         1           163            +++                                                 3           171            +++                                                 8           193            +++                                                 11          227            ++                                                  12          229            ++                                                  13          465            ++                                                  16          476            +                                                   19          228            ++                                                  26          242            +                                                   28          572            ++                                                  41          236            +++                                                 43          172            +++                                                 44          207            +++                                                 76          502            ++                                                  83          523            ++                                                  85          477            +                                                   91          517            +++                                                 94          528            +                                                   100         411            ++                                                  101         555            +                                                   102         551            +++                                                 103         550            ++                                                  104         549            ++                                                  108         541            +                                                   109         561            ++                                                  110         562            ++                                                  111         563            ++                                                  112         564            ++                                                  113         565            +++                                                 114         566            ++                                                  116         568            +                                                   117         570            ++                                                  118         573            ++                                                  119         574            +++                                                 120         575            +++                                                 121         576            +                                                   122         583            +                                                   123         589            ++                                                  124         590            +                                                   125         591            +                                                   126         602            +                                                   127         605            ++                                                  128         618            ++                                                  130         620            ++                                                  131         621            ++                                                  ______________________________________                                          Note                                                                           (a) survival percentage to hypoxic aggression is given according to the        following notation                                                             + from 30 to 49%                                                               ++ from 50 to 79%                                                              +++ higher than or equal to 80%                                           

What is claimed is:
 1. Benzoyl- and α-hydroxybenzyl-phenylglycosides selected from the group consisting of:(i) compounds corresponding to general formula: ##STR8## wherein: Z represents CO or CHOH;X₂, X₃, X₄ and X₅, which are identical or different, each represent hydrogen, halogen, an alkyl group with 1 to 4 carbon atoms, an alkyl group with 1 to 4 carbon atoms substituted by one or more halogen atoms, an OH group, an alkoxy group with 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms substituted by one or more halogen atoms, a nitro group, a cyano group, a thiocyano group, an isothiocyano group, a NR'R" group (where R' and R", which are identical or different, each represent hydrogen or an alkyl group with 1 to 4 carbon atoms); X₁ represents hydrogen, halogen, an alkyl group with 1 to 4 carbon atoms, an alkyl group with 1 to 4 carbon atoms substituted by one or more halogen atoms, an OH group, an alkoxy group with 1 to 4 carbon atoms, an alkoxy group with 1 to 4 carbon atoms substituted by one or more halogen atoms, a nitro group, a cyano group, a thiocyano group, an isothiocyano group, an NR'R" group (where R' and R", which are identical or different, each represent hydrogen or an alkyl group with 1 to 4 carbon atoms), an --NH--CS--O--CH₃ group or an --O--C(CH₃)₂ DO₂ --R'" group (where R'" is an alkyl group with 1 to 4 carbon atoms) and R represents an unsubstituted, non-hydrolyzable monosaccharide carbohydrate radical; or a non-hydrolyzable monosaccharide carbohydrate radical substituted with at least one substituent selected from the group consisting of acyl, alkyl and sulfonyl groups; and (ii) when Z is CHOH, the diastereoisomers of the compounds of (i).
 2. A compound according to claim 1, wherein the hydroxyl and amine functions of the group R are acylated, methylated, benzylated or sulfated.
 3. A compound according to claim 1, wherein X₁, X₂, X₃, X₄ and X₅, identical or different, each represent an alkoxy group having 1 to 4 carbon atoms substituted by a radical selected from the group H, Cl, Br, CH₃, CF₃, OH, OCH₃, NO₂, NH₂, N(CH₃)₂, and NCS; X₁ also representing in para position with respect to the Z group an --OC(CH₃)₂ CO₂ --CH(CH₃)₂ or an --NH--CS--OCH₃ group when X₂, X₃, X₄, and X₅ all represent H; and R represents a non-hydrolyzable, monosaccharide carbohydrate radical selected from the group consisting of β-D-glucosyl, β-D-xylosyl, β-D-galactosyl, and β-D-glucosaminyl, the corresponding carbohydrate radicals in which the hydrogen atom of the OH groups of the carbohydrate radical is replaced by a radical selected from the group consisting of COCH₃, CH₃, CH₂ C₆ H₅, SO₃ HN₄ , SO₃ Na, and SO₃ K, and the corresponding carbohydrate radicals in which the amine function of the carbohydrate radical is substituted by a COCH₃ group.
 4. [4-(4-nitrobenzoyl)-phenyl]-2,3,4-tri-(O-acetyl)-β-D-xylopyranoside.
 5. [4-(4-nitrobenzoyl)-phenyl]-β-D-xylopyranoside.
 6. [3-(4-trifluoromethylbenzoyl)-phenyl]-β-D-xylopyranoside.
 7. [4-(4-chlorobenzoyl)-phenyl]-3,4,6-tri-(ammonium-sulfate)-2-N-acetyl-β-D-glucosaminide.
 8. [4-(4-nitrobenzoyl)-phenyl]-2-N-acetyl-β-D-glucosaminide.
 9. [4-(4-nitro-α-hydroxybenzyl)-phenyl]-β-D-xylopyranoside and its diastereoisomers.
 10. [4-(4-nitro-.alpha.-hydroxybenzyl)-phenyl]-2,3,4-tri-(O-acetyl)-β-D-xylopyranoside.
 11. A therapeutic composition containing in association with a physiologically acceptable excipient, an effective ulcer treating amount of a compound according to claim
 1. 